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Imaging predictors of procedural and clinical outcome in endovascular acute

stroke therapy

Article  in  Neurovascular Imaging · December 2015

DOI: 10.1186/s40809-015-0004-z

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Telischak and Wintermark Neurovascular Imaging (2015) 1:4
DOI 10.1186/s40809-015-0004-z

REVIEW Open Access

Imaging predictors of procedural and clinical

outcome in endovascular acute stroke therapy
Nicholas A. Telischak* and Max Wintermark

Abstract
Acute stroke affects 795,000 people per year in the United States, and eighty-seven percent of these represent
ischemic stroke. New level I evidence has created a need for consistent, effective and rapid triage of stroke patients
to properly select those who will most benefit from endovascular stroke therapy. This review highlights anatomical
factors and imaging signs that are prognostic with respect to stroke outcome and which could aid in the selection
of patients that could most benefit from interventional stroke therapies, as well as exclude patients from therapy
who are at a high risk of complication.
Keywords: Stroke, Endovascular stroke, Perfusion imaging, Clot characteristics, Blood brain permeability, Core infarct

Introduction these trials have resulted in recent randomized controlled

Acute stroke affects 795,000 people per year in the United
States, and eighty-seven percent of these represent ische-
mic stroke. The prevalence of stroke is projected to in-
crease 20.5 % by the year 2030, as a result of an aging
population [1]. While intravenous tissue plasminogen acti-
vator (tPA) has been a mainstay of stroke therapy since its
approval by the Food and Drug Administration in 1996,
interventional treatment of stroke provides the best pos-
sible chance of a good clinical outcome when patients are
appropriately selected, as has recently been borne out by a
handful of randomized controlled trials [2–5]. While this
wealth of new data is very exciting, predicting which pa-
tients will respond best to stroke therapy remains a chal-
lenge. In this review, we aim to highlight imaging findings
prior to stroke therapy that may predict therapeutic and
clinical success.
Clinical trials of endovascular treatment of stroke
Interventional treatment of stroke denotes any catheter-
directed therapy and has progressed from intra-arterial ad-
ministration of tPA to mechanical clot disruption with a
microwire, the MERCI device, suction thrombectomy (e.g.
Penumbra), and use of stent-retriever devices including
Solitaire and TREVO. Initially the IMS III, SYNTHESIS
expansion, and MR RESCUE trials failed to show a clinical
benefit to interventional stroke. Lessons learned from
* Correspondence: teli@stanford.edu
Department of Neuroradiology, S047 300 Pasteur Drive, Stanford, CA 94305, USA
trials overwhelmingly favoring endovascular stroke therapy.
Intra-arterial thrombolysis was originally evaluated in
a randomized-controlled trial using the drug pro-
urokinase in the PROACT II trial, which showed 66 %
recanalization in patients randomized to treatment, but
also showed a relatively high rate of symptomatic intra-
cranial hemorrhage. The clinical outcomes showed no
difference in mortality between groups, and an absolute
increase in favorable outcome of 15 % in the interven-
tional group, corresponding to a number needed to treat
of 7 [6]. The drug used in this trial, urokinase, was
pulled by the FDA due to “significant deviations from
Current Good Manufacturing Practices” [7].
The IMS III trial randomized 656 participants and
showed similar rates of functional independence (mRS 0-2)
of 40.8 % and 38.7 % in the endovascular and IV tPA
groups, respectively, with a trend toward better outcomes
in the endovascular group among patients with National
Institute of Health Stroke Scale (NIHSS) >20 [8]. A strong
criticism of this trial is that less than half of patients got a
CTA resulting in 20 % of patients without a large vessel oc-
clusion being randomized to the interventional arm. Stand-
ard dose IV tPA was not given to the majority of patients
in the interventional arm. Due to the slow trial recruitment,
there were many protocol iterations with many patients re-
ceiving interventional therapy with first-generation devices
that do not have the same efficacy or safety profile as

© 2016 Telischak and Wintermark. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.
Telischak and Wintermark Neurovascular Imaging (2015) 1:4
Table 1 Modified Rankin Scale (mRS) for standardized
evaluation of clinical outcome after stroke
Modified Rankin Clinical Description
Scale (mRS)
0 No symptoms.
1 No significant disability. Able to carry out all
usual activities despite some symptoms.
2 Slight disability. Able to look after own affairs
without assistance, but unable to carry out all
previous activities.
3 Moderate disability. Requires some help, but
able to walk unassisted.
4 Moderately severe disability. Unable to attend to
own bodily needs without assistance. Unable to
walk unassisted.
5 Severe disability. Requires constant nursing care
and attention, bedridden, incontinent.
6 Dead.
today’s stentrievers (40 % recanalization in IMS III versus
68 % -80 % recanalization with modern stentrievers) [8].
The SYNTHESIS expansion trial enrolled 362 pa-
tients with AIS to IV tPA within 4.5 h versus IA ther-
apy within 6 h of symptom onset. No pre-procedural
imaging was required (10 % of patients did not have
a large vessel occlusion), nor was a lower boundary of
NIHSS at presentation defined (nearly half of enrolled
patients had NIHSS scores of 10 or less). Once ran-
domized, 165 of 181 patients in the interventional
arm received an endovascular procedure, and only 56
of these received mechanical thrombectomy. Add-
itionally, the intervention arm received treatment one
hour later on average compared to the IV arm. Suc-
cess of revascularization was not reported. Despite
lack of confirmation of a large vessel occlusion, with-
holding of IV tPA, and the delivery of IA tPA to pa-
tients without a vessel occlusion, there was no
increase in death or intracranial hemorrhage com-
pared to IV tPA. Not surprisingly given these short-
comings, the trial failed to show a benefit in 3 month
mRS in the interventional arm [9].
The Mechanical Retrieval and Recanalization of
Stroke Clots Using Embolectomy (MR RESCUE)
Trial was a multi-center randomized trial comparing
standard medical care to interventional stroke ther-
apy in patients presenting within 8-h with a large
vessel anterior circulation stroke. All patients received
a perfusion MR or CT prior to randomization. Inter-
ventional stroke therapy was not superior to standard
medical care, but this trial did show that patients
with revascularization had improved 3-month mRS
(3.2 versus 4.1) and lower median absolute infarct
growth (9.0 mL vs. 73 mL) [10]. Importantly, MR RESCUE
included first generation thrombectomy devices only, and
Page 2 of 12
achieved a very low reperfusion rate (27 %) compared with
modern trials [10].
Many lessons learned from the shortcomings of these
trials have highlighted the attributes of an ideal candidate
for stroke intervention: 1) A proximal vessel occlusion
that can be reached by an endovascular approach, 2) a
small area of core infarction, and 3) viable tissue at risk of
infarction if reperfusion is not achieved, the ischemic
“penumbra” [11]. This knowledge has resulted in a wealth
of recent trials showing overwhelming benefit of endovas-
cular stroke therapy beginning with the MR CLEAN trial
from the Netherlands.
MR CLEAN enrolled 500 patients with a confirmed
proximal arterial occlusion in the anterior cerebral circu-
lation who could be treated intra-arterially within 6 h of
symptom onset. The majority (89 %) of enrolled patients
were treated with IV-tPA prior to endovascular therapy,
and in the interventional arm four out of five patients
(81.5 %) were treated with retrievable stent devices
resulting in a good rate (58.7 %) of recanalization. Using
modified Rankin scale shift at 90 days, the adjusted com-
mon odds ratio was 1.67 in favor of the intervention [2].
The REVASCAT trial was halted early citing loss of
equipoise after the publication of the MR CLEAN re-
sults. REVASCAT randomized 206 patients with a prox-
imal anterior circulation occlusion without a large
infarct who could be treated within 8 h from symptom
onset to medical therapy alone (IV tPA) or medical ther-
apy and endovascular therapy with the Solitaire stent re-
triever. Ischemic core was estimated by ASPECTS,
admitting patients only with ASPECTS of 6 to 10;
NIHSS was at least 6 for admission into the trial. This
trial showed benefit of endovascular stroke therapy, with
a common odds ratio of 1.7 in the Rankin shift analysis
in favor of endovascular therapy, and 15.5 % absolute
difference in the proportion of patients who were func-
tionally independent at 90 days (43.7 % vs. 28.2 %) [4].
The ESCAPE trial was halted early after an interim ana-
lysis was prompted by the MR CLEAN results. ESCAPE
Table 2 TICI Scoring for assessment of procedural success in
acute stroke therapy
Grade TICI Score
0 No Perfusion.
1 Antegrade reperfusion past the initial occlusion but limited
distal branch filling with little or slow distal reperfusion.
2a Antegrade reperfusion of less than half of the occluded target
artery previously ischemic territory (e.g. 1 major MCA division
and its territory).
2b Antegrade reperfusion of more than half of the previously
occluded target artery ischemic territory.
3 Complete antegrade reperfusion of the previously occluded
target artery without visualized distal occlusion in all distal
branches.
Telischak and Wintermark Neurovascular Imaging (2015) 1:4 Page 3 of 12

Fig. 1 (See legend on next page.)

Telischak and Wintermark Neurovascular Imaging (2015) 1:4
(See figure on previous page.)
Fig. 1 Large ischemic core in a 37-year-old female who awoke with right gaze preference and left sided-weakness. Axial non-contrast computed
tomography (CT) images at the level of the basal ganglia (a) and through the centrum semiovale (b) show hypodensity and loss of grey-white
differentiation of the right insular cortex, putamen, and right frontal grey matter. This is similarly shown by axial diffusion weighted images (c,d).
Cerebral blood volume (CBV) map from the perfusion CT show decreased CBV corresponding to those territories consistent with a large core of
completed infarct (e, f). The Tmax maps demonstrate a matched perfusion deficit (g, h)
recruited 316 patients with a proximal anterior circulation
occlusion and randomized to standard of care with IV tPA
vs. standard of care plus endovascular treatment with
thrombectomy devices up to 12 h from symptom onset.
Patients with large infarct (Alberta Stroke Program Early
CT Score, ASPECTS < 6) or poor collaterals (<50 % filling
of pial collaterals on CTA) were excluded. This study
showed both an improvement in mRS at 90 days in the
interventional arm of 53.0 % vs. 29.3 % as well as a de-
creased mortality in the interventional arm of 10.4 % vs.
19.0 % [5].
The EXTEND-IA trial was also stopped early once the
results of MR CLEAN became available, after recruitment
of 70 patients who were receiving IV tPA within 4.5 h from
symptom onset to interventional treatment with the Soli-
taire stent-retriever device or to continuation of IV tPA
alone. Eligible patients were selected with perfusion-CT
and CT-angiogram to have a proximal anterior circulation
arterial occlusion and an ischemic core of less than 70 mL.
Compared with IV tPA alone, endovascular therapy re-
sulted in a significantly higher probability of reperfusion
(89 % vs. 34 %), and this translated to a significant clinical
benefit with more patients in the interventional arm (71 %
vs. 40 %) achieving functional independence (mRS 0-2) at
90 days [3].
The SWIFT PRIME study enrolled patients with a
NIHSS > 8 resulting from a proximal anterior circula-
tion arterial occlusion and utilized perfusion-CT
with automated software to compute the volume of
core infarct selecting patients with a core <50 cc
(later modified to read baseline evidence of a moder-
ate/large core as defined by ASPECTS < 6). Patients
with a Tmax lesion of >100 cc were excluded (see
malignant perfusion profile, below). The treatment
window in SWIFT PRIME was 6 h. Again, this trial
showed a benefit of endovascular therapy showing a
number needed to treat of only 2.6 for an improved
disability outcome, and of only 4 patients for one
additional patient to be functionally independent at
90 days [12].
Beyond the proven clear benefit of endovascular stroke
therapy, there are lessons to be learned. Three studies
that showed the highest frequency of functional inde-
pendence were the SWIFT PRIME (60 %), the ESCAPE
trial (53 %) and the EXTEND IA trial (71 %). This likely
reflects commonalities among these trials including fast
time to endovascular therapies, exclusion of patients
Page 4 of 12
with large core infarcts on the basis of advanced im-
aging, and higher rates of reperfusion in the endovascu-
lar arms. Advanced imaging clearly plays a role in
patient selection for endovascular stroke therapy; the
goal of this paper is to review predictive signs and mea-
sures of advanced imaging in acute stroke.
Outcome measures in endovascular stroke therapy
Outcome measures in endovascular acute stroke therapy
may be graded with clinical metrics (e.g. mRS at 90 days)
[13, 14], and with imaging metrics (e.g. TICI reperfusion
score) [15]. These are well reviewed elsewhere and are
summarized in Table 1 and Table 2.
There are numerous fixed clinical variables that impact
the outcome of a stroke patient after reperfusion ther-
apy, including presentation NIHSS, baseline functional
status, time from stroke onset to reperfusion, patient
age, patient comorbidities, etc. In this paper, we focus on
imaging findings that can predict procedural success and
clinical outcome.
Results: Imaging predictors of good outcomes in
endovascular stroke therapy
Side of occlusion
The laterality of the stroke has a great effect on patient
outcome, with dominant hemisphere strokes having a
greater impact per volume of infarct than a non-
dominant hemisphere stroke. In a study relating DWI le-
sion volume to poor outcome (mRS >2), the 95 % speci-
ficity lesion volume was 51.8 mL for the left hemisphere
compared to 98.5 mL for right hemisphere involvement,
indicating that non-dominant hemisphere strokes are
better tolerated [16]. While some of this difference re-
lates to an inherent bias of the NIHSS scoring towards
dominant hemisphere stroke, it is clear that a dominant
hemisphere infarct portends a worse prognosis.
Ischemic core estimation
The size of the completed infarct when a patient presents
with a stroke represents irrecoverable damage and there-
fore more than success of recanalization sets the stage for
how much recovery can be expected [17]. Ischemic core
size is an independent predictor of outcome after stroke,
whether measured by CT or DWI MR (Fig. 1) [18–21]. In
a retrospective study, good outcome (mRS 0-2) occurred
with average lesion volumes of 16.3 mL whereas the aver-
age lesion size in poor outcome (mRS >2) was 63.4 mL
Telischak and Wintermark Neurovascular Imaging (2015) 1:4 Page 5 of 12

Fig. 2 Dense middle cerebral artery (MCA) sign with an ischemic penumbra in a 68-year-old male with acute stroke. Non-contrast computed
tomography (CT) demonstrates a dense left MCA with long length of thrombus (a). This manifests “blooming” on gradient recalled echo (GRE, b)
magnetic resonance imaging. CT angiography (CTA) shows a left carotid terminus occlusion extending into the left middle cerebral artery (c), with
a better depiction of collaterals than can be seen on the time-of-flight magnetic resonance angiogram (MRA, d). Diffusion weighted MR image
(DWI, e) and perfusion weighted MRI Tmax map with colorized overlay representing the infarcted core (pink, e) and the territory at risk (green, f),
here showing a favorable perfusion pattern with a small ischemic core and large penumbra

again demonstrating the link between lesion size at presen- stroke is highly correlative with final stroke volume, with
tation and outcome [16]. When measured by MRI at 48 h, normalization of brain tissue previously showing abnormal
the infarct volume is an independent predictor of outcome DWI signal (“DWI reversal”) representing an unlikely
[18]. The estimation of ischemic core by DWI during acute event. When DWI reversal does occur it is not of sufficient
Telischak and Wintermark Neurovascular Imaging (2015) 1:4
size to meaningfully alter the degree of diffusion-perfusion
mismatch [22].
Because MRI is difficult to obtain at many centers alter-
nate methods have been devised to estimate ischemic core
with CT. The Alberta Stroke Program Early CT Score (AS-
PECTS) divides the brain into 10 territories with points re-
moved for loss of grey matter-white matter differentiation
in each territory based on a non-contrast CT evaluation
[23]. This score has been shown repeatedly to correlate
with outcome; for instance when applied to the National
Institute of Neurological Disorders and Stroke (NINDS)
cohort, ASPECTS 8-10 group had a greater benefit from
IV thrombolysis and a trend toward reduced mortality
[24]. In the original study ASPECTS score of 7 or below
demarcated good from poor outcomes [23]. The rate of
change of ASPECTS score in patients transferred to a com-
prehensive stroke center having already undergone a CT
scan at an outside hospital is likely a reflection of collateral
perfusion and is also predictive of outcome [25].
Perfusion CT (PCT) imaging is used at many stroke cen-
ters to triage patients to appropriate therapy because it is
fast to obtain and nearly universally available. The primary
goal of perfusion imaging is to differentiate ischemic core
from the penumbra [26]. Within an ischemic core both
cerebral blood flow (CBF) and cerebral blood volume
(CBV) are lowered; CBV is the most accurate predictor of
the core infarct [27]. A trial investigating whether PCT can
predict response to recanalization, Computed Tomography
Perfusion to Predict Response to Recanalization in Ischemic
Stroke Project (CRISP), is ongoing [28].
Clot location
The location of the occluded vessel has an effect both on
success of revascularization but also on clinical outcomes.
Large vessel occlusion, defined in one study as vertebral,
basilar, internal carotid, proximal (M1 segment) middle
cerebral and proximal (A1 segment) anterior cerebral ar-
tery occlusion, correlates to worse outcome. Specifically,
the odds ratio for mortality is 4.5 and the odds ratio of
good outcome (mRS ≤2) is 0.33 in patients with a large
vessel occlusion compared to those without [29].
In patients treated with IV tPA, the rates of complete re-
canalization for ICA terminus, proximal MCA, and distal
MCA are 5 %, 10 % and 22 %, respectively [30]. In the
SWIFT trial, the ICA, M1 MCA, and M2 MCA made up
21 %, 66 %, and 10 %, respectively, of patients randomized
to the Solitaire device with overall recanalization of 69 %
as assessed by the core laboratory [31]. In TREVO2, rates
of ICA, M1 and M2 enrollment were 16 %, 60 %, and
16 %, respectively, with overall recanalization (TICI ≥2) of
86 % [32]. More proximal occlusions are therefore much
less likely to respond to IV compared to IA therapy. In the
DEFUSE2 trial, using largely first-generation thrombectomy
devices, ICA and MCA occlusions were revascularized with
Page 6 of 12
similar success (61 % and 59 %, respectively) with similar
proportions of good clinical outcome after revascularization
of 65 % for ICA recanalization and 63 % for MCA recanali-
zation [33].
Even when applied to the M1 segment, patients
harboring proximal M1 segment MCA lesions are less
likely to have a good functional outcome compared to
distal M1 segment MCA lesions (8 % vs. 39 %), and are
more likely to sustain a basal ganglia infarct comprising
the internal capsule (83 % vs. 11 %) [34]. A similar study
examined patient outcome based on location of hyper-
dense MCA sign, and showed improved clinical outcome
in distal as compared with proximal sites of occlusion
(85 % vs. 15 % mRS 0-2) [35].
Clot characteristics
Thrombus is most commonly the cause of ischemic
stroke, but not every thrombus is the same. Thrombus
subtype has been stratified into platelet-rich and red
blood cell-rich varieties, and this distinction has been
shown to have an effect on success of tPA and on inter-
ventional stroke therapy [36]. Surrogate markers of clot
composition include density on non-contrast CT, and
the degree of blooming artifact on GRE MR images
(Fig. 2). Dense clots on CT and blooming clots on GRE
MRI both imply a red blood cell predominant compos-
ition. Red cell predominant clots infer a favorable re-
sponse to both IV and IA stroke therapies compared
with clots of lower density or without GRE blooming
artifact [37].
The length of thrombus, also described as clot burden,
has been shown to predict likelihood of recanalization, as
well as final stroke outcome. In one study, no thrombus
exceeding 8-mm in length resulted in recanalization after
treatment with IV tPA [38]. Another study in which 54 %
of patients received IV tPA and the other 46 % received IV
tPA plus IA therapy, recanalization was achieved 85 % of
the time for thrombi <10 mm, 37.5 % for thrombi 10-
20 mm, and in no cases for thrombi >20 mm, demonstrat-
ing that a longer thrombus is more resistant to both IV
and IA therapies [39]. When a “clot burden” score is
Table 3 ASITN/SIR Collateral flow grading system
Grade 0 No collaterals visible to the ischemic site
Grade 1 Slow collaterals to the periphery of the ischemic site
with persistence of some of the defect
Grade 2 Rapid collaterals to the periphery of ischemic site
with persistence of some of the defect and to only
a portion of the ischemic territory
Grade 3 Collaterals with slow but complete angiographic blood
flow of the ischemic bed by the late venous phase
Grade 4 Complete and rapid collateral blood flow to the vascular
bed in the entire ischemic territory by retrograde
perfusion
Telischak and Wintermark Neurovascular Imaging (2015) 1:4 Page 7 of 12

Fig. 3 (See legend on next page.)

Telischak and Wintermark Neurovascular Imaging (2015) 1:4
(See figure on previous page.)
Fig. 3 Favorable collaterals in a 67-year-old with acute right MCA occlusion. Axial maximum intensity projection (MIP) of the CTA show a right
M1 segment MCA occlusion (a) with excellent collateral filling of the affected territory (a, b). Correlative CTP shows no CBV evidence of a
completed core infarct (c, d). A large ischemic penumbra is evident on the Tmax maps (e, f). Colorized threshold maps demonstrate a small
region of core infarct (pink, g) with a relatively large territory at risk (green, h)
allocated for thrombotic occlusion of vascular territories,
increasing clot burden is associated with both worse func-
tional outcome as well as with larger final infarct as
assessed by ASPECTS score [40]. Looking forward, im-
aging may serve as a tool to better define clot constituents
and help guide treatment decisions based on probability of
success for a given clot composition.
Collateral scoring
In ischemic stroke, neuronal loss occurs at an average
rate of 1.9 million per minute [41]. While this number is
grossly simplified, it speaks to the exquisite sensitivity of
a neuron to oxygen debt. It therefore stands to reason
that collateral flow is a critical factor in determining
both the rate of stroke completion and the extent of in-
volvement of the affected hemisphere. A recent review
cited 63 different methods of assessing collateral flow,
however the most commonly used method, developed
by the American Society of Interventional and Therapeutic
Neuroradiology (ASITN) and the Society of Interventional
Radiology (SIR) is summarized in Table 3 [42].
High quality collaterals have been shown to be inde-
pendent predictors of both favorable outcome and re-
canalization (Fig. 3) [43–46]. When applied to stroke, a
malignant profile representing a complete lack of collat-
eral vessels in the affected territory, is a discriminator of
lesion volume >100 mL (itself a strong predictor of out-
come), and of being functionally dependent (mRS ≥ 3) at
3 months [47].
Good collaterals are a strong predictor of recanalization;
conversely patients with poor collaterals are less likely to
achieve recanalization and more likely to have hemorrhagic
transformation [48, 49]. In the ENDOSTROKE study, bet-
ter collateral vessels (ASITN/SIR grades of 0 or 1, 2, and 3
or 4) were associated with higher reperfusion rates (21 %,
48 %, and 77 %), a higher proportion of infarcts smaller
than one-third of the MCA territory (32 %, 48 %, and
69 %), and a higher proportion of good clinical outcome
(11 %, 35 %, and 49 %) [50].
In the ESCAPE trial of endovascular stroke therapy, in
addition to proof of small infarct core and proximal ves-
sel occlusion, patients were selected on the basis of a
moderate to good collateral score, which has also been
shown to be an independent predictor of outcome after
stroke [5, 51]. Good patient selection in this trial clearly
contributed to the favorable treatment results, highlight-
ing the value of collateral scoring.
Page 8 of 12
Penumbra imaging
Estimate of the ischemic penumbra in acute stroke in rela-
tion to the core infarct is a critical piece of information
when triaging candidates for interventional stroke therapy.
While ischemic penumbra is present in 90 % to 100 % of
patients with anterior circulation stroke in a three hour
window, 75 % to 80 % continue to have some degree of
penumbral tissue at 6 h [26]. Selecting patients with pre-
served tissue at risk prevents futile reperfusion of infarcted
tissue and improves outcomes in stroke therapy [2–5]. In-
deed, recent trials that selected patients for endovascular
stroke therapy with perfusion imaging show the largest
benefit [2, 3]. This estimate may be made clinically using
the NIHSS as a surrogate marker of ischemia, but using
PCT imaging adds specificity and reproducibility to this es-
timate (Fig. 4). Penumbral information as assessed by PCT
provides information that cannot be inferred clinically, and
is an independent predictor of stroke outcome. An import-
ant point with respect to perfusion imaging is a finding
termed the malignant profile, which denotes a large lesion
with markedly delayed perfusion as defined by a DWI
core > 100 mL or a perfusion-weighted image lesion of
100 mL or more with Tmax delay of 8 s or more. The ma-
lignant profile is associated with poor outcome and a
higher rate of symptomatic intracranial hemorrhage after
interventional stroke therapy (Fig. 5) [52].
White matter injury
Diffusion tensor imaging (DTI) allows visualization of
white matter tracts, the injury of which has prognostic
value in acute stroke. For instance, the integrity of the
corticospinal tract as assessed by MRI can predict the
probability of motor recovery after corona radiata stroke
[53–55]. In the acute stage, diffusion tractography pre-
dicted motor function at 90 days better than clinical
scores [55].
Blood-brain barrier (BBB) permeability
Symptomatic intracranial hemorrhage is a complica-
tion of endovascular stroke therapy with an incidence
ranging from 0-7.7 % in recent trials [2–5]. This can
have important consequences for final outcome after
endovascular stroke therapy and therefore it is im-
portant to have imaging metrics to prospectively ex-
clude patients who are at a high risk of hemorrhage
from endovascular therapies. The hyperintense acute
reperfusion marker (HARM) is an early marker of
BBB breakdown, observed as hyperintense signal seen
Telischak and Wintermark Neurovascular Imaging (2015) 1:4 Page 9 of 12

A B

C D

E F

G H
Fig. 4 (See legend on next page.)
Telischak and Wintermark Neurovascular Imaging (2015) 1:4 Page 10 of 12

(See figure on previous page.)

Fig. 4 Large ischemic penumbra with small core infarct in a 73 year-old with acute stroke. MRA shows acute M1 segment MCA vessel cutoff
(arrow, a). Blooming artifact localizes to the occlusive thrombus on the GRE image (arrow, b). Apparent diffusion coefficient (a, d, c) map (c, d)
demonstrating a small region of core infarct (arrowhead). CBV maps from the PCT show no region of decrease to suggest a large core infarct
(e, f). Ischemic penumbra comprises the majority of the left MCA territory on the Tmax maps (g, h)

Fig. 5 Malignant perfusion profile in an 82-year-old with a right MCA syndrome. MRA showing a right M1 segment MCA occlusion (a). GRE image
demonstrates blooming from thrombus at the site of occlusion (b, arrow). DWI image demonstrates a moderate-sized ischemic core (c), which is
colorized on the perfusion map (pink, d). The ischemic penumbra is larger than the ischemic core (green, e) but in this instance is notable for a
large volume of Tmax > 10s consistent with a malignant perfusion profile (f)
Telischak and Wintermark Neurovascular Imaging (2015) 1:4
on FLAIR hours to days after gadolinium administra-
tion believed to be caused by accumulation of con-
trast material in the CSF spaces, and is associated
with higher rates of hemorrhagic transformation of
stroke [56]. Unfortunately since HARM is seen hours
to days after an initial MRI, this is not useful for tri-
age of interventional therapies. Blood brain barrier
permeability increases with increasing neuronal injury
as a result of ischemia-induced break down of tight
junctions, and can be measured with perfusion im-
aging as expressed by a permeability surface area
product (PS). This tool can prospectively stratify pa-
tients into those who will or will not go on to de-
velop hemorrhagic conversion using a PS threshold of
0.23 mL/min/100 g [57]. Another study observed an
odds ratio of 28 for hemorrhagic transformation dis-
criminating with a PS of >0.84 mL/100 g/min [58].
While not in widespread use, this information is in
theory readily available in centers that triage stroke
with perfusion imaging.
Conclusion
Level I evidence showing a powerful benefit for endovas-
cular stroke therapy makes this an exciting time for endo-
vascular stroke therapy. On the other hand this evidence
has created a need for consistent, effective and rapid triage
of stroke patients to properly select those who will most
benefit from endovascular stroke therapy. Recent trials
have highlighted the need to select patients for endovascu-
lar stroke therapy based on the presence of a proximal ar-
terial occlusive lesion, a small-to-moderate sized core
infarct, and evidence of ischemic penumbra. While this is
simple and quick to perform, it is not nuanced and many
other useful imaging predictors of stroke outcome are not
taken into consideration in such a simple model. This re-
view has highlighted specific anatomical factors, imaging
signs, and stroke physiology that have predictive value in
the setting of the triage of a patient presenting with acute
stroke. Looking forward, these imaging-specific factors
could be included along with demographic factors such as
patient age and baseline functional status in a more com-
prehensive prognostic model to assist in the triage of
stroke patients.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
MW and NT each contributed to text. All authors read and approved the
final manuscript.
Received: 9 June 2015 Accepted: 30 June 2015
Page 11 of 12
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